By I. Chenor. University of Alaska, Fairbanks.

For the immediate-release tablets diarex 30 caps for sale, the dosage is 150 mg every 8 hours initially generic 30caps diarex overnight delivery, and can be gradually increased to 300 mg every 8 hours buy diarex 30 caps with mastercard. For the extended-release capsules diarex 30 caps otc, the dosage is 225 mg every 12 hours initially, and can be gradually increased to 425 mg every 12 hours. B l a c k B o x Wa r n i n g : P ro p a f e n o n e Because of its prodysrhythmic actions, propafenone should be reserved for patients who have not responded to safer drugs. At this time only four beta blockers—propranolol, acebutolol, esmolol, and sotalol—are approved for treating dysrhythmias. It is worth noting that cardiac beta receptors are functionally coupled to1 calcium channels and that beta blockade causes these channels to close. Because beta blockers and calcium channel blockers both decrease calcium entry, the cardiac effects of these drugs are very similar. Therapeutic Use Propranolol is especially useful for treating dysrhythmias caused by excessive sympathetic stimulation of the heart. Among these are sinus tachycardia, severe recurrent ventricular tachycardia, exercise-induced tachydysrhythmias, and paroxysmal atrial tachycardia evoked by emotion or exercise. In patients with asthma, blocking beta receptors in the2 lung can cause bronchospasm. In addition, each drug can affect the heart in other ways, and so they are not interchangeable. Ibutilide is availiable intravenously only, and is therefore discussed in Chapter 89. Because of toxicity, amiodarone is approved only for life-threatening ventricular dysrhythmias that have been refractory to safer agents. Nonetheless, because of its efficacy, amiodarone is one of our most frequently prescribed antidysrhythmic drugs, used for atrial and ventricular dysrhythmias alike. Indications, electrophysiologic effects, time course of action, and adverse effects differ for each route. Although amiodarone is very effective, concerns about toxicity limit its indications. In the United States oral amiodarone is approved only for long-term therapy of two life-threatening ventricular dysrhythmias: recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia. Amiodarone is our most effective drug for atrial fibrillation and is prescribed widely to treat this dysrhythmia—even though it is not approved for this use. The drug is given to convert atrial fibrillation to normal sinus rhythm and to maintain normal sinus rhythm after conversion. These occur secondary to blockade of sodium channels, calcium channels, and beta receptors. Amiodarone also acts on coronary and peripheral blood vessels to promote dilation. Amiodarone is highly lipid soluble and accumulates in many tissues, especially the liver and lungs. Because of its slow elimination, amiodarone continues to act long after dosing has ceased. B l a c k B o x Wa r n i n g : P u l m o n a r y To x i c i t y Lung damage—hypersensitivity pneumonitis, interstitial/alveolar pneumonitis, pulmonary fibrosis—is the greatest concern. Pulmonary toxicity develops in 2% to 17% of patients and carries a 10% risk for mortality. Accordingly, thyroid function should be assessed at baseline and periodically during treatment. B l a c k B o x Wa r n i n g : L i v e r To x i c i t y Amiodarone can injure the liver. Accordingly, tests of liver function should be obtained at baseline and periodically throughout treatment. If circulating liver enzymes exceed 3 times the normal level, amiodarone should be discontinued. Signs and symptoms of liver injury, which are seen only rarely, include anorexia, nausea, vomiting, malaise, fatigue, itching, jaundice, and dark urine. Rarely, amiodarone has been associated with optic neuropathy and optic neuritis, sometimes progressing to blindness. Patients who develop changes in visual acuity or peripheral vision should undergo ophthalmologic evaluation. If optic neuropathy or neuritis is diagnosed, discontinuation of amiodarone should be considered. Fortunately, these deposits have little or no effect on vision and so rarely necessitate amiodarone cessation. Amiodarone crosses the placental barrier and enters breast milk and can thereby harm the developing fetus and breastfeeding infant. Accordingly, pregnancy and breastfeeding should be avoided while using the drug and for several months after stopping it. Patients frequently experience photosensitivity reactions (skin reactions triggered by exposure to ultraviolet radiation). To reduce risk, patients should avoid sunlamps and should wear sunblock and protective clothing when outdoors. Fortunately, this discoloration resolves within months after amiodarone is discontinued. Interactions of concern include the following: • Amiodarone can increase levels of several drugs, including quinidine, procainamide, phenytoin, digoxin, diltiazem, warfarin, cyclosporine, and three statins: lovastatin, simvastatin, and atorvastatin. Oral amiodarone [Cordarone, Pacerone] is available in tablets (100, 200, and 400 mg). The following schedule is used for loading: 800 to 1600 mg daily for 1 to 3 weeks, followed by a daily maintenance dosage of 200-600 mg. The drug is indicated for oral therapy of atrial flutter and paroxysmal or persistent atrial fibrillation, but not permanent atrial fibrillation. The manufacturer hoped to create a drug with the high efficacy of amiodarone, but with less toxicity. Unfortunately, although dronedarone is somewhat less toxic than amiodarone, it is also less effective. Dronedarone has a much shorter half-life than amiodarone, so adverse effects resolve more quickly. Pharmacokinetics Oral bioavailability is low in the absence of food (4%) and higher in the presence of food (15%). The elimination half-life is 13 to 19 hours—much shorter than the 25 to 110 days seen with amiodarone. As a result, steady-state levels are achieved fairly quickly with dronedarone (4–8 days) versus 1 to 5 months with amiodarone. Adverse Effects The most common side effects are diarrhea, weakness, nausea, and skin reactions. In contrast to amiodarone, dronedarone does not cause significant thyroid toxicity, pulmonary toxicity (e. Dronedarone can increase skin sensitivity to sunlight, but it does not cause the bluish-gray skin discoloration seen with amiodarone. Furthermore, because dronedarone has a much shorter half-life than amiodarone, adverse effects that do occur have a much shorter duration.

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Tere is an association with primigravida order 30caps diarex free shipping, obesity generic diarex 30caps with amex, multiple pregnancies and male foetuses (ratio 3:1) cheap diarex 30caps without a prescription. Also there is no robust evidence about the relationship between the foetal risks and the maternal serum bile acid levels generic diarex 30 caps on line. Hepatitis B vaccination is recommended, and the woman’s immune status should be determined preconceptually. Renal and liver function tests should be performed annually to identify sickle nephropathy and/or deranged hepatic function. Tere is no randomised evidence on whether routine screening should be performed or if patients should be screened only if they experience visual symptoms, but we recommend that women are screened preconceptually. In women who have been multiply transfused in the past or who have a high ferritin level, T2* cardiac magnetic resonance imaging may be helpful to assess body iron loading. Aggressive iron chelation before conception is advisable in women who are signifcantly iron loaded. Red cell antibodies may indicate an increased risk of haemolytic disease of the newborn. It should be avoided in the frst trimester due to lack of safety evidence, but can be continued afer 20 weeks’ gestation in low doses. The pneumococcal vaccine should be given every 5 years, whereas haemophilus infuenza type b and conjugated meningococcal C vaccine should be given as a single dose once. The possible causes of thrombocytopenia in pregnancy include pregnancy-associated or gestational thrombocytopenia (75%), hypertensive pathology (15%–20%), immune causes (3%–4%) and others (1%–2%). So, Ventouse delivery is best avoided as this may be associated with neonatal intraventricular haemorrhage if foetal platelets are low. Close liaison with the haematology team is necessary in planning the management of this type of case. Additional reading Reducing the risk of venous thromboembolism during pregnancy and puerperium. Recent prospective and retrospective family studies support the view that defciencies of the naturally occurring anticoagulants (antithrombin, protein C and protein S) are of greater clinical signifcance than heterozygous carriage of factor V Leiden or the prothrombin gene mutation. Additional reading Reducing the risk of venous thromboembolism during pregnancy and puerperium. Advise pregnant women with diabetes who are on insulin or glibenclamide to maintain their capillary plasma glucose level above 4 mmol/L. Target blood glucose levels preconception period Advise women with diabetes who are planning to become pregnant to aim for the same capillary plasma glucose target ranges as recommended for all people with type 1 diabetes: a fasting plasma glucose level of 5–7 mmol/L on waking and a plasma glucose level of 4–7 mmol/L before meals at other times of the day. Explain to women with diabetes who are planning to become pregnant that establishing good blood glucose control before conception and continuing this throughout pregnancy will reduce the risk of miscarriage, congenital malformation, stillbirth and neonatal death. Ofer a trial of changes in diet and exercise to women with gestational diabetes who have a fasting plasma glucose level below 7 mmol/L at diagnosis. Ofer metformin to women with gestational diabetes if blood glucose targets are not met within 1–2 weeks using changes in diet and exercise. A 30-year-old woman with a previous history of caesarean section and multiple uterine fbroids had a repeat elective caesarean section due to breech presentation. Anti-D prophylaxis should be administered in which one of the options, if she had the following blood products transfused? A 20-year-old, nulliparous woman at 12 weeks’ gestation attends her antenatal booking appointment. Which one of the following questionnaires was recommended to assess the mental health and well-being of the woman? A 28-year-old para 1 woman with history of bipolar disorder and previous postpartum psychosis attends her antenatal clinic appointment at 14 weeks’ gestation. A 30-year-old nulliparous woman was treated for an early stage breast cancer 2 years ago and is currently taking tamoxifen. A 28-year-old nulliparous woman was diagnosed with an early stage breast cancer at 12 weeks of pregnancy. How long should she be considered potentially infectious afer exposure to chickenpox? She attends antenatal clinic at 28 weeks’ gestation and says that she had a recurrence of genital herpes 2 weeks ago, which has now resolved. Steroids + erythromycin + oral acyclovir + delivery by caesarean section at 34 weeks b. Steroids + erythromycin + intravenous acyclovir + delivery by caesarean section at 34 weeks c. Steroids + erythromycin + oral acyclovir + consider induction of labour at 34 weeks d. Steroids + erythromycin + intravenous acyclovir + consider induction of labour at 34 weeks e. A 42-year-old, para 4 woman with pre-eclampsia comes to antenatal clinic at 34 weeks’ gestation. She is asymptomatic with stable blood pressures on labetalol and the biochemical markers are normal. She is extremely anxious as she had abruption in her previous pregnancy that has led to an emergency caesarean section at 34 weeks’ gestation. Which one of the risk factors has the most predictive value for abruption in this pregnancy? A 38-year-old para 3 woman with three previous caesarean sections has attended her frst antenatal clinic appointment. What is her risk for placenta praevia in comparison to women with no previous caesarean sections? A gravida 4 para 2 woman attends at 32 weeks’ gestation with history of ruptured membranes. She had cervical cerclage placed at 13 weeks’ gestation because of two previous preterm deliveries and one second trimester loss. A nulliparous woman was referred to the day assessment unit afer an incidental fnding of a cervical length of 18 mm with funnelling at 23 weeks’ gestation by the sonographer. A nulliparous woman at 35 weeks was found to have polyhydramnios with an amniotic fuid index of 28 cm. A nulliparous woman at 35 weeks’ gestation was referred for a scan as large for gestational age. The foetal growth was normal with no obvious foetal structural anomalies, but there was unexplained polyhydramnios with an amniotic fuid index of 29 cm. Tere was signifcant discrepancy in the amniotic fuid volume with a maximum vertical pool of 1. You are seeing a 32-year-old para 2 woman at 16 weeks’ gestation in the antenatal clinic. She had two previous normal vaginal deliveries, but sustained a third-degree tear during her second delivery.

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Warn patients against abruptly discontinuing beta blockers because this may cause tachycardia and other dysrhythmias order diarex 30 caps amex. Advise patients order 30caps diarex, when traveling order diarex 30caps on-line, to carry an adequate supply of medication plus a copy of their prescription discount 30caps diarex mastercard. Prescribing and Monitoring Considerations Alpha -Adrenergic Antagonists 1 Alfuzosin Doxazosin Prazosin Silodosin Tamsulosin Terazosin Therapeutic Goal Doxazosin, Prazosin, Terazosin These drugs reduce blood pressure in patients with essential hypertension. Identifying High-Risk Patients The only contraindication is hypersensitivity to these drugs. Ongoing Monitoring and Interventions Evaluating Therapeutic Effects Essential Hypertension. Patients need to move slowly when changing from a supine or sitting position to an upright posture. Beta-Adrenergic Antagonists Acebutolol Atenolol Betaxolol Bisoprolol Carteolol Carvedilol Esmolol Labetalol Metoprolol Nadolol Nebivolol Pindolol Propranolol Sotalol Timolol Except where noted, the implications here apply to all beta-adrenergic blocking agents. Therapeutic Goal Principal indications are hypertension, angina pectoris, heart failure, and cardiac dysrhythmias. Angina Pectoris Determine the incidence, severity, and circumstances of anginal attacks. Use with caution (especially the nonselective agents) in patients with asthma, bronchospasm, diabetes, or a history of severe allergic reactions. Use all beta blockers with caution in patients with a history of depression and in those taking calcium channel blockers. Advise patients to record the incidence, circumstances, and severity of any anginal attacks. Abrupt withdrawal of beta blockers can cause tachycardia and ventricular dysrhythmias. By blocking alpha-adrenergic receptors, carvedilol and labetalol can cause postural hypotension. As mentioned previously, these alpha-adrenergic effects may be minimized by having patients sit or lie down if these occur. Patients need to move slowly when changing from a supine or sitting position to an upright posture. Beta blockade can mask early signs and symptoms of hypoglycemia by1 preventing common tachycardia, tremors, and perspiration. Patients will need to rely on indicators such as hunger and poor concentration to identify hypoglycemia. It may be necessary to monitor fingerstick glucose more closely until recognition is well-established. Beta blockade can prevent glycogenolysis,2 an emergency means of increasing blood glucose. Cardioselective beta blockers are preferred to nonselective agents in patients with diabetes. Maternal use of betaxolol during pregnancy may cause bradycardia, respiratory distress, and hypoglycemia in the infant. Accordingly, for 3 to 5 days after birth, newborns should be closely monitored for these effects. If these occur, switching to a beta blocker with low lipid solubility may help (see Table 14. Two calcium channel blockers—verapamil and diltiazem—can intensify the cardiosuppressant effects of the beta blockers. Beta blockers can prevent the compensatory glycogenolysis that normally occurs in response to insulin-induced hypoglycemia. With both groups, the net result is reduced activation of peripheral adrenergic receptors. Hence the pharmacologic effects of the indirect-acting adrenergic blocking agents are very similar to those of drugs that block adrenergic receptors directly. Why are we discussing centrally acting drugs in a unit on peripheral nervous system pharmacology? Because the effects of these drugs are ultimately the result of decreased activation of alpha- and beta-adrenergic receptors in the periphery. P a t i e n t E d u c a t i o n Clonidine Advise the patient to take the major portion of the daily dose at bedtime to minimize daytime sedation. For transdermal clonidine, instruct the patient to apply transdermal patches to hairless, intact skin on the upper arm or torso, and to apply a new patch every 7 days. Have patient record blood pressure daily and call the clinic if hypotension develops. Warn patients against abruptly discontinuing beta blockers because this may cause tachycardia and other dysrhythmias. Advise patients, when traveling, to carry an adequate supply of medication plus a copy of their prescription. Inform patients that discomfort can be reduced by chewing sugarless chewing gum, sucking hard candy, and taking frequent sips of fluids. Clonidine is not used as often as many antihypertensive drugs; however, it has important indications in the management of severe hypertension. Except for rare instances of rebound hypertension, the drug is generally free of serious adverse effects. By activating central alpha2 receptors, clonidine reduces sympathetic outflow to blood vessels and to the heart. Pharmacologic Effects The most significant effects of clonidine concern the heart and vascular system. By suppressing the firing of sympathetic nerves to the heart, clonidine can cause bradycardia and a decrease in cardiac output. By suppressing sympathetic regulation of blood vessels, the drug promotes vasodilation. The net result of cardiac suppression and vasodilation is decreased blood pressure. Because the hypotensive effects of clonidine are not posture dependent, orthostatic hypotension is minimal. Hypotensive responses begin 30 to 60 minutes after administration and peak in 4 hours. Clonidine is eliminated by a combination of hepatic metabolism and renal excretion. About 35% of patients experience drowsiness; an additional 8% experience outright sedation. Patients in their early weeks of treatment should be advised to avoid hazardous activities if alertness is impaired. Patients should be advised that discomfort can be reduced by chewing gum, sucking hard candy, and taking frequent sips of fluids. Rebound Hypertension Rebound hypertension is characterized by a large increase in blood pressure occurring in response to abrupt clonidine withdrawal. This rare but serious reaction is caused by overactivity of the sympathetic nervous system and can be accompanied by nervousness, tachycardia, and sweating. If blood pressure climbs dangerously high, it should be lowered with a combination of alpha- and beta-adrenergic blocking agents.

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